English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/130510
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Spatial and temporal diversity in genomic instability processes defines lung cancer evolution

AuthorsBruin, Elza C. de; Gerlinger, Marco; Varela, Ignacio ; Swanton, Charles
Issue Date2014
PublisherAmerican Association for the Advancement of Science
CitationScience 346(6206): 251-256 (2014)
AbstractSpatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis.We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.
DescriptionPMCID: PMC4636050.-- et al.
Publisher version (URL)http://dx.doi.org/10.1126/science.1253462
URIhttp://hdl.handle.net/10261/130510
DOI10.1126/science.1253462
Identifiersdoi: 10.1126/science.1253462
e-issn: 1095-9203
issn: 0036-8075
Appears in Collections:(IBBTEC) Artículos
Files in This Item:
File Description SizeFormat 
lung cancer evolution.pdf1,5 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.